Ingested food is first broken down mechanically into pieces that can be swallowed, then into small particles that can pass out of the stomach into the small intestine. Small particles contain the major nutrients in our diet: carbohydrates, protein, and fat. Enzymes digest small particles into components that can be absorbed. In this topic, we will study the enzymes that digest each of these major nutrients. First let’s study the digestion of carbohydrates. The most abundant dietary carbohydrates are starch and the three disaccharides: sucrose (or table sugar), lactose (or milk sugar), and maltose (or grain sugar). Carbohydrates are built from monosaccharides and must be digested to their component monosaccharides so they can be absorbed. In our representative molecules, geometric symbols represent single monosaccharides. Starch is digested to glucose. Sucrose is digested to Glucose and Fructose Lactose is digested to Glucose and Galactose. Maltose is digested to Glucose. Now let’s study the digestion of protein. Proteins are digested to amino acids and small peptide chains of two or three amino acids. In our representative protein, each circle represents a single amino acid. Now let’s study the digestion offat. Most dietary fat consists of triglycerides. Triglycerides are digested to monoglycerides and free fatty acids. In our representative triglyceride, the three circles represent the carbons of a glycerol backbone and the picket fences represent fatty acids. Remember that no polar products of digestion can be absorbed across the intestinal epithelium by simple diffusion, a passive process. In general, polar substances are absorbed by carrier-mediated transport. Carrier-mediated transport may be active requiring the energy of ATP, or passive relying on the concentration gradient of the substance being absorbed. Plant starch and glycogen (animal starch) are the most abundant dietary carbohydrates. Carbohydrates are long polymers of glucose. Digestion of starch begins in the mouth with salivary amylase, which is maximally active at about pH 7. Amylase breaks starch down to the disaccharide maltose, to fragments of three glucose molecules called maltotriose, and to small, branched fragments called limit dextrins. In our illustration, each hexagon represents a glucose molecule. The hexagons at branch points represent glucose-glucose links that are not hydrolyzed by amylase. Digestion begins with salivary amylase. Amylase continues to work in the stomach until food is mixed with gastric juice and acidified. Acid denatures amylase. In the stomach, pepsin begins the digestion of protein. Proteins are long polymers of amino acids. Pepsin is the only major digestive enzyme that is maximally active at acidic pH. Pepsin cleaves proteins that bonds between the amino acids tyrosine and phenylalanine, producing peptide fragments and a small amount of individual amino acids. In this illustration, each circle represents an amino acid. Pepsin is active only in the stomach. When chyme is neutralized in the duodenum, pepsin is denatured. Most digestion and almost all absorption occurs in the small intestine. The pancreas supplies the digestive enzymes for most foodstuffs. Neither salivary amylase nor pepsin is essential for digestion. Pancreatic enzymes alone are adequate to digest carbohydrates and protein. There is little digestion of fat until it reaches the small intestine. Pancreatic lipase is essential for fat digestion; without it malabsorption of fat occurs. Humans lack digestive enzymes for the plant polysaccharide cellulose and some other complex carbohydrates. Vegetables and fruits are good sources of vitamins, minerals and other nutrients. The indigestible polysaccharides contained in vegetables and fruits make up dietary fiber. Fiber increases bulk of the stool and promotes its timely movement through the colon. Let’s observe salt and water absorption. Most of the salt and water that enter the GI tract are absorbed in the small intestine. Salt and water may be absorbed by transcellular transport through intestinal epithelial cells or by paracellular transport through leaky tight junctions between cells. Paracellular transport is passive and keeps the total osmolarity of the intestinal contents similar to the osmolarity of blood plasma. Transcellular transport of fluid depends on active transport of sodium. Sodium potassium pumps in the basal lateral membrane pump sodium out of intestinal epithelial cells to keep the intracellular concentration of sodium low and to elevate the concentration of sodium in the interstitial fluid. Sodium enters epithelial cells at the luminal surface cotransported with glucose or amino acids through sodium ion channels and on several other transporters moving down its electrochemical gradient. Chloride follows sodium absorption, increasing the amount of salt in the interstitial space. The osmotic pressure generated by the movement of salt and other solutes into the interstitial space causes water to follow by osmosis. These transport mechanisms are similar to salt and water transport mechanisms in the proximal tubule of the kidney and may be reviewed in the urinary system module. The small intestine has the capacity to absorb more food than is usually ingested at one time. Increased intake causes increased absorptive capacity. It is almost impossible to exceed the absorptive capacity of the small intestine. We will study absorption of the end products of the digestion of major nutrients next. The carbohydrates that enter the small intestine for digestion include: starch, its breakdown products from salivary amylase digestion, and the dietary disaccharides: sucrose (table sugar), lactose (milk sugar), and maltose (grain sugar). Pancreatic amylase continues the breakdown of starch in the lumen. It is identical to salivary amylase and maximally active at about pH 7. Since only monosaccharides are absorbed, the breakdown products of starch and the disaccharides must be digested further. Brush border enzymes accomplish this job. A brush border enzyme called glucoamylase, that lies close to the sodium-glucose cotransporter, breaks down maltose and maltotriose. A brush border enzyme called dextrinase breaks down small, branched segments of starch. It also lies close to the sodium-glucose cotransporter. Brush border enzymes also break down sucrose and lactose. Sucrose is broken down by the brush border enzyme called Sucrase. And Lactose is broken down by a brush border enzyme called Lactase. Most nutrients are absorbed by transepithelial transport moving first into the intestinal epithelial cells at their luminal surface then out at their basal surface. Glucose and galactose enter intestinal cells, cotransported with sodium, by the process of secondary active transport. Notice that both glucose and galactose use the same transporter. Fructose enters intestinal cells on a fructose-specific transporter by the process of facilitated diffusion. All monosaccharides leave epithelial cells on a common transporter by the process of facilitated diffusion. Notice that glucose, galactose, and fructose use the same transporter. They enter capillaries for transport in the blood. Ingested proteins, peptides from pepsin digestion, proteins from sloughed cells, and enzymes enter the small intestine for digestion. Trypsin, chymotrypsin, and carboxypeptidase, the major pancreatic proteases, continue protein digestion in the lumen. These enzymes are maximally active at about pH 7. Trypsin and chymotrypsin cleave proteins into smaller peptides and some single amino acids. Carboxypeptidase cleaves one amino acid at a time from the carboxyl end of a protein. Dipeptides and tripeptides, as well as single amino acids, are absorbed. Aminopeptidase and dipeptidase continue the digestion of peptides. Many single amino acids enter intestinal cells cotransported with sodium by the process of secondary active transport. There are several different amino acid transporters. Transport of some amino acids does not require sodium. Most protein is absorbed as di- and tripeptides. Small peptide cotransporters use secondary active transport, some driven by sodium, others by hydrogen ions. Di- and tripeptides are broken down to amino acids inside the cells. Some amino acids leave epithelial cells by diffusion. The more hydrophobic the amino acid, the more likely it is to leave by diffusion. Other amino acids leave cells by facilitated diffusion or cotransport with sodium. Triglycerides are the most abundant dietary fat. They are made from a glycerol molecule to which three fatty acids are attached. Fatty acids may be short, medium, or long chains of carbon and hydrogen. Almost all fat digestion occurs in the small intestine. Pancreatic lipase breaks down triglycerides; it is maximally active at about pH 7. Since fat is insoluble in water, it tends to aggregate in large drops, leaving little surface area for lipase to work. Segmentation in the small intestine breaks the large drops into smaller drops, and disperses those drops throughout the chyme. Segmentation in the small intestine does to chyme what shaking does to a bottle of oil and vinegar salad dressing. It disperses the fat layer into the aqueous layer. Notice what happens when you set the jar down after shaking it. Bile salts in the intestine keep the small fat droplets in solution by a process called emulsification. The function of bile salts is directly related to their structure. They are hydrophobic on one side, their steroid core and hydrophilic on the other side primarily due to the presence of hydroxyl groups. Keeping the small fat droplets in solution provides a large surface area for lipase action. Lipase digests triglycerides to monoglycerides and free fatty acids Another function of bile salts is to surround the cleaved products, forming tiny droplets called micelles. Micelles are a million times smaller than emulsified fat droplets. When micelles are in close proximity to the cell membrane, monoglycerides and fatty acids move out of them to enter intestinal cells by simple diffusion through the lipid bilayer. Triglycerides are reassembled inside the cells and packaged into chylomicrons that are coated with lipoproteins to keep them emulsified. Chylomicrons leave the cell by exocytosis. Since they are too large to pass through the basement membrane of capillaries, they enter lymph vessels called lacteals. Short chain and medium chain fatty acids are absorbed by simple diffusion, and can directly enter capillaries. However, the normal diet contains few fatty acids of these chain lengths.